Abstract 4485: Synthesis of targeted docetaxel-polymer conjugate and its anti-tumor efficacy

Over the last decade, it has been shown that nanopolymer therapeutics can be engineered to target cancer cells specifically and can deliver the cancer agent in a time-release fashion, thereby leaving normal healthy cells unaffected by toxic drugs such as docetaxel. Docetaxel has been used to treat several types of cancers, but it has provided pharmaceutical challenges due to its poor solubility and toxicities associated with the co-solvents. Given that nanotechnology can enhance the specificity, efficacy and safety of cancer agents and with the need of a new alternative formulation for docetaxel delivery, we developed a poly N-(2-hydroxypropyl) methacrylamide (HPMA)-Docetaxel (Doc) conjugate with Folate (FA) targeting ligand and evaluated the effect of the product in both in vitro human cancer cell lines and in vivo mice xenograft tumor models. Analysis of the product displayed the incorporation of 7.9% of docetaxel and 2.1% of folate with 38.6kDa MW and 1.92 of polydispersity, and an improvement in water solubility. The product inhibited the proliferation of a variety of human cancer cells in nM ranges in in vitro study. The maximal tolerated dose (MTD) of the product in mice was more than 150 mg/kg (as a docetaxel amount), which is much higher than that of free docetaxel (∼25 mg/kg). In mice bearing tumor xenografts, treatment with the polymer-conjugate strongly inhibited the growth of various human tumors, extended survival, and enhanced tumor regression significantly without effects on body weight compared to control animals. The results clearly demonstrate that our new polyHPMA-docetaxel-folate conjugate compound is a promising candidate for anti-tumor chemotherapeutics with reduced toxicity and prolonged survival. Citation Format: Young Bok Lee, Deog Joong Kim, Miyoung Yang, Chang-Ho Ahn, Anjan Nan. Synthesis of targeted docetaxel-polymer conjugate and its anti-tumor efficacy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4485. doi:10.1158/1538-7445.AM2014-4485